Age-dependent VDR peak DNA methylation as a mechanism for latitude-dependent multiple sclerosis risk.

Autor: Ong LTC; Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW, 2145, Australia. lawrence.ong@sydney.edu.au.; Department of Immunology, Westmead Hospital, Cnr Darcy and Hawkesbury Rds, Westmead, NSW, 2145, Australia. lawrence.ong@sydney.edu.au., Schibeci SD; Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW, 2145, Australia., Fewings NL; Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW, 2145, Australia., Booth DR; Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW, 2145, Australia., Parnell GP; Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW, 2145, Australia.
Jazyk: angličtina
Zdroj: Epigenetics & chromatin [Epigenetics Chromatin] 2021 Feb 04; Vol. 14 (1), pp. 9. Date of Electronic Publication: 2021 Feb 04.
DOI: 10.1186/s13072-021-00383-x
Abstrakt: Background: The mechanisms linking UV radiation and vitamin D exposure to the risk of acquiring the latitude and critical period-dependent autoimmune disease, multiple sclerosis, is unclear. We examined the effect of vitamin D on DNA methylation and DNA methylation at vitamin D receptor binding sites in adult and paediatric myeloid cells. This was accomplished through differentiating CD34+ haematopoietic progenitors into CD14+ mononuclear phagocytes, in the presence and absence of calcitriol.
Results: Few DNA methylation changes occurred in cells treated with calcitriol. However, several VDR-binding sites demonstrated increased DNA methylation in cells of adult origin when compared to cells of paediatric origin. This phenomenon was not observed at other transcription factor binding sites. Genes associated with these sites were enriched for intracellular signalling and cell activation pathways involved in myeloid cell differentiation and adaptive immune system regulation.
Conclusion: These results suggest vitamin D exposure at critical periods during development may contribute to latitude-related differences in autoimmune disease incidence.
Databáze: MEDLINE
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